Summary Human papillomaviruses (HPV) are the most common sexually transmitted infection in the US. Upon infection individuals make a low-titer antibody response to conformational epitopes on the L1 protein. Most HPV infections are controlled or cleared, however in some individuals infection can persist and give rise to neoplastic lesions. Highly efficacious vaccines are in widespread use to prevent human papillomavirus (HPV) disease. Our previous studies have focused on polyclonal antibody responses in subjects who were naturally infected or who had been vaccinated. Given new approaches that we have developed, we now have the ability to more fully characterize the B cell memory repertoire, including plasmablasts (PB), B memory cells (Bmem) and human monoclonal antibodies isolated from Bmem and PB. We will study the basis of antibodies neutralizing activity as well as other possible mechanisms of protection. It is an important goal to determine the signatures that may be associated with long term protection of a vaccine given to adolescents or pre- adolescents that will need protection for several decades. The efficacy trials of HPV vaccines have all delivered three doses of vaccine but there is considerable interest in switching to two or fewer doses. We will examine the B cell memory responses obtained from an ongoing trial comparing two doses vs three doses of the new nine-valent HPV vaccine.